P-090: IS A DEDICATED MARKETING APPROVAL OF HYDROXYUREA IN SICKLE CELL DISEASE MAY INCREASE THE CLINICAL BENEFIT OF THE DRUG?
Authors: GALACTÉROS F., VOSKARIDOU E., HABIBI A., CANNAS G., JOSEPH L., LOKO G., DE MONTALEMBERT M.
Journal: HemaSphere (2022)

Purpose: The first marketing approval of hydroxyurea in SCD was granted in US in 1998 in adults. 10 years after EMA gave a marketing approval in SCD in children from 2 years old. In 2017 in US HU was approved in children. However, in the majority of African countries, in Brazil or in India where the SCD population is important hydroxyurea is not approved in SCD, but only in myeloproliferative disorders and in adults only. Is there an interest in patients and clinicians to have hydroxyurea products dedicated to the SCD? Materials and methods: Escort HU (European Sickle Cell Disease Cohort – Hydroxyurea) is a non-interventional prospective cohort study conducted in patients treated with HU according to current clinical practice with SCD. The main objective was to refine the safety profile of hydroxycarbamide, but clinical effectiveness were evaluated by recording painful crises lasting more than 48 hours, episodes of ACS, number of hospitalisations related to SCD, and biological parameters were also regularly recorded according to the frequency of the hospital visits. Results: At inclusion, 926 (48.7%) patients had been previously treated off the label with HU (as HU was only approved for myeloproliferative disorders at the time), with mean duration of HU treatment of 5.74 ± 4.98 years. The mean age of this subgroup was 27.60 ± 14.81 years compared to 19.75 ± 15.79 years of the patients never been treated with HU before enrolment As showed in the Table 1, hemoglobin level remains unchanged during the first two years but the HbF% increased in the HU-pretreated subgroup. In the “HU-naïve group”, despite lower baseline Hb level et HbF% at baseline, similar outcome were obtained after 12 or 24 months. In terms of clinical outcomes, after 1 year of treatment the number of vaso-occlusive crises (VOC), acute chest syndrome (ACS) or hospitalizations decreased dramatically (Table 2) in both group. The median duration of follow-up in the cohort was 45 months (0-128). 123.7 ± 62.7 months. In term of safety, neutropenia, thrombocytopenia and dry skin were the most frequent HU- related adverse events reported but with comparable cumulated incidence between the HU-pretreated subgroup and HU-naïve subgroup (Table 3). Conclusion: In real life setting, a significant improvement of the vaso-occlusive symptoms was observed even in patients previously treated with HU for a long time. It was observed an improvement of compliance and consequently of effectiveness as suggested by the lower MCV than expected, at baseline in patients previously treated with HU. Paule and al (2011) demonstrated that daily regimen of HU could be superior in term of efficacy to weekly regimen. The fine tuning of the daily dose possible with HU tablets might be another reason of clinical optimization. Even hydroxyurea is available for SCD patients, dedicated marketing approvals of the drug for SCD patients seem support the compliance of the patients materialized by better clinical benefits. These data may encourage Health authorities and pharmaceutical companies to develop and to approve drugs in the indication and so to avoid off-label uses.Table 1 Biological parameters in the subgroups after 12 and 24 months Table 2. Number of VOC, ACS and hospitalizations after 1 year of HU treatment in the cohort compared to the previous year before enrolmentTable 3. Most Frequent Adverse Events Sorted by Relative Risk by Previous HU Treatment Other Than HU tablets E. VOSKARIDOU declares a conflict of interest: Consultancy, Expert: Addmedica: Consultancy Invitation to national or international congresses: NO Patent or product inventor: NO Research support/Scientific studies: PARTICIPATION OF THE SITE IN HU-ESCORT STUDY AND HU ESCORT STUDY EXTENTION Stock shareholder: NO Trainings, Teaching: NO